Effect of stress-like concentrations of cortisol on gonadotroph function in orchidectomized sheep

The effect of stress-like concentrations of cortisol (C) on the feedback potency of estradiol (E-2) was assessed using 32 orchidectomized sheep (wethers) assigned at random to 1 of 4 treatment groups in a 2 x 2 factorial design. Wethers received C (3.6 mg/50 kg per hour; groups 2 and 4) or a comparable volume of C delivery vehicle (groups 1 and 3) as a continuous infusion for 7 days. During the final 48 h of infusion, wethers received E-2 (0.3 mu g/50 kg/h; groups 3 and 4) or E-2 delivery vehicle (groups 1 and 2). The pattern of LH secretion was assessed during a 4-h period of intensive blood collection beginning 44 h after initiation of E-2 infusion. Gonadotroph responsiveness (LH secretion induced by GnRH challenge [500 ng, i.v.]) was determined 48 h after E-2 delivery was begun. Although the frequency of secretory episodes of LH was not affected (p > 0.05) by infusion of C or E-2 alone, LH pulse frequency was significantly decreased in wethers receiving C and E-2 in combination. In contrast, neither the magnitude of basal gonadotroph responsiveness nor the extent of E-2-dependent augmentation of responsiveness was significantly affected by stress-like concentrations of C, In a second experiment, the effect of C on the magnitude of E-2-induced increase in pituitary concentration of GnRH receptor and GnRH receptor mRNA was assessed using 32 additional wethers, Continuous infusion of E-2 for 48 h increased (p < 0.05) tissue concentrations of GnRH receptor and GnRH receptor mRNA. Concurrent delivery of C did not affect (p > 0.05) E-2-induced increase in GnRH receptor mRNA but significantly reduced the magnitude of the E-2-dependent increase in pituitary concentration of GnRH receptor, Collectively, these data indicate that stress-like concentrations of C enhance the negative feedback potency of E-2 and reduce estrogen-dependent augmentation of the concentration of GnRH receptor in pituitary tissue.